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BARD1c.2127A>GUncertain significance
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Variant interpretation report

BARD1 c.2127A>G, p.(Pro709=)

NM_000465.4:c.2127A>G NP_000456.2:p.(Pro709=) View identifiers
Classification
Uncertain significance

Variant description:

No variant summary was recorded for this case.

Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About BARD1

No gene-level summary was recorded for this case.

LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.
01The reasoning

How it was classified

The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 0 Benign evidence criteria: 1
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 1
BP7Supporting
BP7 · supporting

This variant is a synonymous change, NM_000465.4:c.2127A>G (p.Pro709=), and SpliceAI predicts no significant splice impact with a maximum delta score of 0.00. Available evidence is consistent with no effect on splicing or protein sequence, so BP7 is met at supporting strength.

Recorded classification: Uncertain significance

Generic ACMG/AMP 2015 final-classification combination rules were used as the applicable fallback framework because no usable official VCEP/CSPEC or local custom gene-specific final-classification framework was present.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

gnomAD v4.1
gnomAD v2.1
Population frequency
Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

No listed criterion applied
gnomAD v4.1 ↗gnomAD v2.1 ↗
No screenshot for this evidence
Computational predictions
Not recorded

No SpliceAI or REVEL score is recorded in the fields used for this tile.

Applied · BP7 →
ClinVar submissions
Not recorded

A ClinVar laboratory submission summary was not recorded.

Context only ClinVar ↗
Functional evidence
Statement recorded

OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).

No listed criterion applied OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
Not assessed

No COSMIC evidence statement is recorded in this case.

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only Cancer Hotspots ↗
For specialists

Technical detail

ACMG/AMP criteria under Not recorded, with the data and sources behind each one.

28 criteria with recorded statuses: 1 met · 6 not met · 12 not assessed · 9 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

The BARD1 c.2127A>G (p.Pro709=) variant has not been observed in somatic cancers in COSMIC and has been reported in ClinVar with Likely benign and Benign submissions.

This variant is absent from gnomAD v2.1 and gnomAD v4.1, with an observed allele frequency of 0, which is below the benign frequency thresholds and does not by itself support pathogenicity for a synonymous variant.

In silico analysis predicts no meaningful splice effect, with a SpliceAI maximum delta score of 0.00, and the variant is synonymous at p.Pro709=, supporting BP7 and not supporting PP3.

Met · 1

BP7 SupportingThis variant is a synonymous change, NM_000465.4:c.2127A>G (p.Pro709=), and SpliceAI predicts no significant splice impact with a maximum delta score of 0.00. Available evidence is consistent with no effect on splicing or protein sequence, so BP7 is met at supporting strength. Details ▾Hide ▴
Rule
BP7 applies to a synonymous variant with no predicted impact on splicing and no expected effect on the protein.
Evidence considered
  • NP_000456.2:p.(Pro709=)
  • SpliceAI max delta 0.00
Still missing
  • No experimental RNA study was identified.
Sources
prefetchcase_summaryspliceai ↗screen_BP734242744

Not met · 6 · evaluated, threshold not reached

PS4 Available evidence does not show that this variant is enriched in affected individuals compared with controls. No case-control data, no quantified excess of affected carriers, and no COSMIC somatic observations were identified, so PS4 is not met. Details ▾Hide ▴
Rule
PS4 applies when the prevalence of the variant in affected individuals is significantly increased over controls.
Evidence considered
  • ClinVar variation 820770
  • COSMIC no result
Still missing
  • Case-control or robust case series data for this specific variant were not available.
Sources
clinvar ↗cosmicscreen_PS41560462817508274181631312436637624366402253941752849253231429903340120683424274435802134
PM1 This variant has not been shown to occur in a well-established critical functional domain or mutational hotspot without benign variation. Cancer Hotspots did not identify a statistically significant hotspot at residue P709, so PM1 is not met. Details ▾Hide ▴
Rule
PM1 applies to variants in a mutational hot spot or critical functional domain without benign variation.
Evidence considered
  • Cancer Hotspots: no significant hotspot at P709
Sources
hotspots ↗case_summary
PM2 This variant is absent from gnomAD v2.1 and gnomAD v4.1, but absence from population databases alone does not establish pathogenicity for a synonymous variant; PM2 is therefore not met. Details ▾Hide ▴
Rule
PM2 applies when a variant is absent or extremely rare in population databases in a manner supportive of pathogenicity.
Evidence considered
  • gnomAD v2.1 absent
  • gnomAD v4.1 absent
Sources
gnomad_v2 ↗gnomad_v4 ↗
PP3 Available in silico evidence does not support a deleterious effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, and the REVEL score is 0.123, so PP3 is not met. Details ▾Hide ▴
Rule
PP3 applies when multiple computational tools support a deleterious effect on the gene or gene product.
Evidence considered
  • SpliceAI max delta 0.00
  • REVEL 0.123
Sources
spliceai ↗prefetchscreen_PP334242744
BA1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, so its observed population frequency is 0 and is below the benign stand-alone threshold of 1%; BA1 is not met. Details ▾Hide ▴
Rule
BA1 applies when allele frequency is above the stand-alone benign threshold.
Evidence considered
  • gnomAD v2.1 AF 0
  • gnomAD v4.1 AF 0
Sources
gnomad_v2 ↗gnomad_v4 ↗
BS1 This variant is absent from gnomAD v2.1 and gnomAD v4.1, so its observed population frequency is 0 and is below the benign strong threshold of 0.3%; BS1 is not met. Details ▾Hide ▴
Rule
BS1 applies when allele frequency is greater than expected for the disorder.
Evidence considered
  • gnomAD v2.1 AF 0
  • gnomAD v4.1 AF 0
Sources
gnomad_v2 ↗gnomad_v4 ↗

Not assessed · 12 · no assessment recorded

PS2 No confirmed de novo occurrence with verified maternity and paternity was identified, so PS2 was not assessed. Details ▾Hide ▴
Rule
PS2 applies to a confirmed de novo variant in a patient with the disease and no family history.
Still missing
  • Parental testing or a documented proven de novo occurrence was not available.
PS3 No well-established functional studies demonstrating a damaging effect of this specific variant were identified, so PS3 was not assessed. Details ▾Hide ▴
Rule
PS3 applies when well-established functional studies support a damaging effect on the gene or gene product.
Still missing
  • Variant-specific validated functional evidence was not available.
Sources
evidenceliterature_pass
PM6 No assumed de novo occurrence without confirmed parentage was identified, so PM6 was not assessed. Details ▾Hide ▴
Rule
PM6 applies to an assumed de novo variant without confirmation of parentage.
Still missing
  • Family-based de novo data were not available.
PP1 No segregation data were identified for this variant, so PP1 was not assessed. Details ▾Hide ▴
Rule
PP1 applies when a variant cosegregates with disease in multiple affected family members.
Still missing
  • Family segregation studies were not available.
Sources
literature_pass
PP4 No phenotype or family history information specific enough to support a highly specific BARD1-related presentation was identified, so PP4 was not assessed. Details ▾Hide ▴
Rule
PP4 applies when the patient's phenotype or family history is highly specific for a disease with a single genetic etiology.
Still missing
  • Clinical phenotype and family history details were not available.
PP5 ClinVar lists this variant as Likely benign and Benign, not pathogenic, and current ACMG/AMP practice does not use database assertions alone to apply PP5; PP5 was therefore not assessed. Details ▾Hide ▴
Rule
PP5 applies to a pathogenic assertion from a reputable source when the primary evidence is not available; this criterion is not used here.
Evidence considered
  • ClinVar: Likely benign/Benign submissions
Sources
clinvar ↗1560462817508274181631312436637624366402253941752849253231429903340120683424274435802134
BS2 No evidence was identified showing this variant in healthy adult individuals in a context sufficient to apply BS2, so BS2 was not assessed. Details ▾Hide ▴
Rule
BS2 applies when a variant is observed in healthy adults for a fully penetrant dominant disorder or at an expected frequency for a recessive disorder.
Still missing
  • Unaffected carrier data were not available.
BS3 No well-established functional studies demonstrating no damaging effect for this specific variant were identified, so BS3 was not assessed. Details ▾Hide ▴
Rule
BS3 applies when well-established functional studies show no damaging effect on the gene or gene product.
Still missing
  • Variant-specific validated functional studies showing no damaging effect were not available.
Sources
evidenceliterature_pass
BS4 No non-segregation data were identified for this variant, so BS4 was not assessed. Details ▾Hide ▴
Rule
BS4 applies when the variant does not segregate with disease in affected family members.
Still missing
  • Family segregation data were not available.
BP2 No phase information demonstrating this variant in trans with a pathogenic variant for a dominant disorder, or in cis for any disorder, was identified, so BP2 was not assessed. Details ▾Hide ▴
Rule
BP2 applies when a variant is observed in trans with a pathogenic variant for a dominant disorder or in cis for any inheritance pattern.
Still missing
  • Phase data were not available.
BP5 No alternate molecular explanation for the phenotype was identified in the available evidence, so BP5 was not assessed. Details ▾Hide ▴
Rule
BP5 applies when an alternate molecular basis for disease has been established.
Still missing
  • Clinical testing context and alternate molecular findings were not available.
BP6 Although ClinVar includes Likely benign and Benign submissions for this variant, database assertions alone were not used to apply BP6; BP6 was not assessed. Details ▾Hide ▴
Rule
BP6 applies to a benign assertion from a reputable source when the primary evidence is not available; this criterion is not used here.
Evidence considered
  • ClinVar: 2 Likely benign laboratories and 1 Benign laboratory
Sources
clinvar ↗28492532
Not applicable · 9· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AThis variant is a synonymous substitution, NM_000465.4:c.2127A>G (p.Pro709=), and does not create a predicted loss-of-function allele; PVS1 is therefore not applicable. Details ▾Hide ▴
Rule
PVS1 applies to predicted loss-of-function variants in a gene where loss of function is a known disease mechanism.
Evidence considered
  • NM_000465.4:c.2127A>G
  • NP_000456.2:p.(Pro709=)
Sources
prefetchcase_summary34242744
PS1 N/AThis variant does not change the amino acid sequence and is not a missense change matching a known pathogenic amino acid substitution, so PS1 is not applicable. Details ▾Hide ▴
Rule
PS1 applies when the variant results in the same amino acid change as an established pathogenic variant.
Evidence considered
  • NP_000456.2:p.(Pro709=)
Sources
prefetchcase_summary
PM3 N/ANo recessive disease context or trans observation relevant to PM3 was identified for this variant, so PM3 is not applicable. Details ▾Hide ▴
Rule
PM3 applies to recessive disorders when the variant is detected in trans with a pathogenic variant.
PM4 N/AThis variant does not change protein length and is not an in-frame insertion or deletion, so PM4 is not applicable. Details ▾Hide ▴
Rule
PM4 applies to protein length changes due to in-frame deletions/insertions or stop-loss variants.
Evidence considered
  • NP_000456.2:p.(Pro709=)
Sources
prefetchcase_summary
PM5 N/AThis variant is not a novel missense change at an amino acid residue with a different established pathogenic missense change, so PM5 is not applicable. Details ▾Hide ▴
Rule
PM5 applies to a novel missense change at a residue where a different pathogenic missense change has been seen before.
Evidence considered
  • NP_000456.2:p.(Pro709=)
Sources
prefetchcase_summary
PP2 N/AThis variant is not a missense change, so PP2 is not applicable. Details ▾Hide ▴
Rule
PP2 applies primarily to missense variants in genes with a low rate of benign missense variation and where missense variation is a common disease mechanism.
Evidence considered
  • NP_000456.2:p.(Pro709=)
Sources
prefetchcase_summary
BP1 N/AThis variant is synonymous rather than missense, so BP1 is not applicable. Details ▾Hide ▴
Rule
BP1 applies to missense variants in genes where truncating variants are primarily pathogenic.
Evidence considered
  • NP_000456.2:p.(Pro709=)
Sources
prefetchcase_summary
BP3 N/AThis variant is not an in-frame insertion or deletion in a repetitive region, so BP3 is not applicable. Details ▾Hide ▴
Rule
BP3 applies to in-frame deletions/insertions in repetitive regions without known function.
Evidence considered
  • NM_000465.4:c.2127A>G
Sources
prefetchcase_summary
BP4 N/AFor this synonymous variant, benign computational evidence is more appropriately captured under BP7 rather than BP4, so BP4 was not applied separately. Details ▾Hide ▴
Rule
BP4 applies when multiple computational tools suggest no impact on the gene or gene product; this evidence was not counted separately from BP7 here.
Evidence considered
  • SpliceAI max delta 0.00
  • REVEL 0.123
Sources
spliceai ↗prefetch

Identifiers

Gene
BARD1
Transcript
NM_000465.4
Coding (HGVS c.)
NM_000465.4:c.2127A>G
Protein (HGVS p.)
NP_000456.2:p.(Pro709=)
GRCh38
chr2:214728883 T>C
GRCh37
chr2:215593607 T>C

Gene diagram

Every interpreted variant in BARD1, mapped onto the exon structure of NM_000465.4. Select a row to find it on the plot.

BARD1NM_000465.4
Fetching transcript structure from UCSC…
gnomAD v4.1 Allele count data not recorded
gnomAD v2.1 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

BP7 SupportingThis variant is a synonymous change, NM_000465.4:c.2127A>G (p.Pro709=), and SpliceAI predicts no significant splice impact with a maximum delta score of 0.00. Available evidence is consistent with no effect on splicing or protein sequence, so BP7 is met at supporting strength. Details ▾Hide ▴
Rule
BP7 applies to a synonymous variant with no predicted impact on splicing and no expected effect on the protein.
Evidence considered
  • NP_000456.2:p.(Pro709=)
  • SpliceAI max delta 0.00
Still missing
  • No experimental RNA study was identified.
Sources
prefetchcase_summaryspliceai ↗screen_BP734242744
PP3 Available in silico evidence does not support a deleterious effect. SpliceAI predicts no significant splice impact with a maximum delta score of 0.00, and the REVEL score is 0.123, so PP3 is not met. Details ▾Hide ▴
Rule
PP3 applies when multiple computational tools support a deleterious effect on the gene or gene product.
Evidence considered
  • SpliceAI max delta 0.00
  • REVEL 0.123
Sources
spliceai ↗prefetchscreen_PP334242744
BP4 N/AFor this synonymous variant, benign computational evidence is more appropriately captured under BP7 rather than BP4, so BP4 was not applied separately. Details ▾Hide ▴
Rule
BP4 applies when multiple computational tools suggest no impact on the gene or gene product; this evidence was not counted separately from BP7 here.
Evidence considered
  • SpliceAI max delta 0.00
  • REVEL 0.123
Sources
spliceai ↗prefetch

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

0 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Captured SpliceAI source record Open source ↗
ClinVar Captured ClinVar source record Open source ↗
COSMIC Captured COSMIC source record
Cancer hotspots Captured Cancer Hotspots source record Open source ↗
OncoKB Captured OncoKB source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

ClinVar

This variant has been reported in ClinVar as Likely benign (2 clinical laboratories) and as Benign (1 clinical laboratory).

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).

Functional

OncoKB oncogenicity for this specific variant: Unknown Oncogenic Effect (variant has not been individually curated).

Somatic

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.